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Purpose: The purpose of this study was to investigate the value of C-11 methionine (MET) positron emission tomography (PET)/computed tomography (CT) in patients with intracranial germinoma (IG)., Material and Methods: We conducted a retrospective analysis of 21 consecutive patients with pathologically confirmed IGs and eight patients with intracranial non-germinomas (INGs) located in a similar region. Clinical characteristics, imaging findings, and tumor markers such as α-fetoprotein (AFP) and β-human chorionic gonadotropin (HCG) were used as clinical variables. Maximum standardized uptake value (SUVmax), tumor-to-normal tissue (T/N) ratio, and visual scoring of tumor were used as MET PET parameters., Results: All IGs were well visualized on MET PET with a three-grade visual scoring system. In addition, SUVmax of IGs was higher than that of INGs (P = 0.005). Pre-treatment (Pre-Tx) T/N ratio was significantly correlated with pre-Tx serum HCG (P = 0.031). Moreover, MET PET parameters showed significant associations with tumor location, sex, KRAS variant, and symptoms., Conclusion: MET PET/CT could be a useful diagnostic tool in patients suspected of having IGs. In addition, the MET avidity of tumor is a potential surrogate biomarker of HCG, which has been used as a diagnostic marker for IGs. Tumor MET parameters also had significant differences according to tumor locations, sex, symptoms, and KRAS mutation. However, MET avidity of tumors had no significant prognostic value., Competing Interests: The authors have declared that no competing interests exist.

Purpose: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities., Materials and Methods: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole brain (WB), and whole ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months., Results: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in 10 patients (5.3%) with a latency of 20 years (range, 4 to 26 years) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction., Conclusion: De-intensifying extended-field rather than involved-field or total scheme of RT will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.

Purpose: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx)., Methods and Materials: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis., Results: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively., Conclusions: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Whether craniospinal irradiation (CSI) could be replaced by limited-field radiation in non-metastatic bifocal germinoma remains controversial. We addressed the issue based on the data from our series and the literature., Materials and Methods: Data from 49 patients diagnosed with non-metastatic bifocal germinoma at our hospital during the last 10 years were collected. The Pediatric Quality of Life Inventory 4.0 was used to evaluate health-related quality of life (HRQOL). Additionally, 81 patients identified from the literature were also analyzed independently., Results: In our cohort, 34 patients had tumors in the sellar/suprasellar (S/SS) plus pineal gland (PG) regions and 15 in the S/SS plus basal ganglia/thalamus (BG/T) regions. The median follow-up period was 52 months (range, 10 to 134 months). Our survival analysis showed that patients treated with CSI (n=12) or whole-brain radiotherapy (WBRT; n=34) had comparable disease-free survival (DFS; p=0.540), but better DFS than those treated with focal radiotherapy (FR; n=3, p=0.016). All 81 patients from the literature had tumors in the S/SS+PG regions. Relapses were documented in 4/45 patients treated with FR, 2/17 treated with whole-ventricle irradiation, 0/4 treated with WBRT, and 1/15 treated with CSI. Survival analysis did not reveal DFS differences between the types of radiation field (p=0.785). HRQOL analysis (n=44) in our cohort found that, compared with S/SS+PG germinoma, patients with BG/T involvement had significantly lower scores in social and school domains. However, HRQOL difference between patients treated with CSI and those not treated with CSI was not significant., Conclusion: In patients with non-metastatic bifocal germinoma, it is rational that CSI could be replaced by limited-field radiation. HRQOL in patients with BG/T involvement was poorer.

Purpose: Intracranial germ cell tumors (ICGCTs) comprise approximately 0.4%-3% of all brain tumors. In this study, we aim to evaluate clinical characteristics, treatment and outcomes of patients with ICGCT., Patients and Methods: All patients with ICGCT diagnosed in Hacettepe University's Pediatric Oncology Department between January 1980 and January 2016 were evaluated, retrospectively., Results: We identified 52 patients (male/female: 2.46) diagnosed with ICGT. Median age was 140 months. The median duration of symptoms was 3 months. Patients with endocrine symptoms were diagnosed later than others (P = 0.028). The primary site was pineal region in 20 patients, nonpineal region in 32 which included six bifocal involvements. Pineal location was more common in boys than girls (P = 0.02). Histopathological diagnosis was germinoma in 28 patients, nongerminomatous malignant germ cell tumors in 14 and immature teratoma in 4. The mean age for germinoma was higher than that of nongerminomatous tumors (P = 0.032). Patients treated with surgery and radiotherapy and chemotherapy. Median follow-up time was 52.5 months. Thirty-six patients were alive for 12-228 months. Relapsed/progressive disease was observed in 11 patients. Nongerminomatous tumors more frequently showed relapse/progression than germinoma (P = 0.06). Five-year overall and event-free survival rates for the whole group were 72.6% and 57.2%, respectively. Overall and event-free survival rates for germinoma were better than malignant nongerminomatous tumors., Conclusion: Although the ratio of ICGCTs to central nervous system tumors in our series was similar to western countries, some clinical features such as tumor location were similar to cases from East Asian countries. Although similar protocols were used survival rates lower than developed western and eastern developed countries., Competing Interests: None

Purpose: The aim of this study was to determine the practice patterns and outcomes of intracranial germ cell tumors (IGCT) in adolescents and young adults according to different therapeutic approaches., Methods and Materials: One-hundred twelve patients with IGCT aged 15 to 39 years were managed at either XX or the XY center from 1975 to 2015. The charts were retrospectively reviewed and data collected., Results: Median duration of follow-up was 8.3 years. Ninety-four patients had germinomas, and 18 had nongerminomatous germ cell tumors (NGGCT). The primary disease sites were pineal gland (37 of 94 germinoma, 14 of 18 NGGCT) and suprasellar region (23 of 94 germinoma, 2 of 18 NGGCT). Eleven patients with germinoma (12%) and 2 patients with NGGCT (11%) had radiographic spinal metastases or positive lumbar cerebrospinal fluid cytology. Event-free survival (EFS) was 84% and overall survival (OS) was 90% at 10 years for germinoma; EFS was 71% and OS was 86% at 10 years for NGGCT. For patients with germinoma, 10-year EFS was 100% after craniospinal radiation therapy (CSRT) with chemotherapy (N = 10); 100% after whole-ventricular radiation therapy (WVRT), whole-brain radiation therapy (WBRT), or focal radiation therapy (FRT) with chemotherapy (N = 22); 90% after CSRT alone (N = 46); and 41% after WVRT, WBRT, or FRT alone (N = 16) (P < .0005). Ten-year OS was 100%, 100%, 90%, and 72%, respectively (P = .032). For patients with NGGCT, 10-year EFS was 80% after CSRT, WBRT, or WVRT plus chemotherapy (N = 10) versus 58% after FRT plus chemotherapy (N = 8) (P = .31); 10-year OS was 90% versus 58%, respectively (P = .16)., Conclusions: We report excellent overall outcomes according to treatment approach in the largest study of IGCT in adolescents and young adults to our knowledge. EFS and OS were inferior after non-CSRT without chemotherapy in germinoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the “good prognosis” group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the “intermediate and poor prognosis” group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24–30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28–261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.

Purpose: To perform a retrospective analysis of patients with intracranial germinoma treated in our department to evaluate treatment outcomes and determine optimal treatment strategies., Methods: We reviewed the treatment outcomes of 170 patients with intracranial germinoma who were treated in our department from January 1996 to January 2017. The median patient age was 15 years old. Among the patients, 56 (33%) were pathologically diagnosed, and 114 (67%) were diagnosed clinically. Various radiation fields and doses were used. Cerebrospinal fluid (CSF) and serum beta-human chorionic gonadotropin (β-HCG) levels were examined before treatment in 114 patients. Endocrinological evaluation was performed in 141 patients before and after treatment. A total of 38 patients received chemotherapy prior to radiotherapy (RT). The median follow-up time was 64.5 months (range 4-260.5 months)., Results: The 5- and 10-year overall survival (OS) rates were 94.5% and 91.3%, respectively. The relapse-free survival (RFS) rates at 5- and 10-years were 91.9% and 78.1%, respectively. Relapses occurred in 18 patients within 6 months-10 years. The spinal cord metastasis rate was 3.4% in patients with a localized lesion who did not receive spinal cord irradiation and 16.7% in patients with bifocal disease who were treated using whole ventricular irradiation (WVI) or whole brain radiotherapy (WBRT). Treatment failure did not occur in patients receiving chemoradiotherapy or in patients receiving three-dimensional conformal radiation therapy (3D-CRT)/intensity-modulated radiation therapy (IMRT). The RFS rate did not have a statistically significant correlation with the CSF/serum β-HCG level. After RT, 19.1% of the patients developed newly impaired pituitary function and required hormone replacement therapy., Conclusions: WVI or WBRT+ primary boost (PB) is a sufficient irradiation field for localized intracranial germinoma, while patients with bifocal disease should undergo craniospinal irradiation (CSI), especially when treated with RT alone. CSF β-HCG is not a prognostic marker for intracranial germinomas. The treatment results of chemotherapy followed by reduced-dose RT are comparable to those of RT alone. IMRT is recommended for intracranial germinoma to improve the target volume accuracy and decrease the complications of RT.

Background: Intracranial germ cell tumors (IGCTs) are a group of rare pediatric brain tumors which include various subtypes. The current understanding of the etiology of the tumors and their optimal management strategies remain controversial., Data Sources: The data on IGCTs were collected from articles published in the past 20 years, and the origin and etiology of IGCTs at molecular level as well as the relative roles of varied treatment strategies in different prognosis groups according to Matsutani's classification were reviewed., Results: Recent cellular and molecular evidence suggests that IGCTs may arise from the transformation of endogenous brain cells; and findings in the molecular characterization of IGCTs suggest roles of CCND2, RB1, and PRDM14 in the pathogenesis of IGCTs and identify the KIT/RAS and AKT1/mTOR pathways as potential therapeutic targets in future. According to Matsutani's classification of IGCTs, the good prognosis group includes both germinomas and mature teratomas. For germinomas, both radiation alone and reduced-dose radiotherapy in combination with adjuvant chemotherapy are effective, while complete surgical excision is recommended for mature teratomas. In the intermediate prognosis group, immature teratoma has been successfully treated with gamma knife surgery. However, for intermediate prognosis IGCTs other than immature teratomas, gross total resection with adjuvant chemotherapy and radiotherapy or gamma knife surgery may be necessary to achieve cure. In the poor prognosis group, survival outcomes are unsatisfactory, and complete surgical resection combined with more intensive chemotherapy and radiotherapy remains the best available treatment option at this time., Conclusions: IGCTs should be strictly classified according to their pathological categories before administering pathology-specific treatments. Although open microsurgical excision is the traditional surgical strategy for IGCTs, recent publications also support the role of endoscopic surgical options for pineal region IGCTs.

Background: Pediatric and young adult central nervous system (CNS) germinomas have favorable cure rates. However, long-term follow-up data are limited because of the rarity of this tumor. We report the long-term overall survival (OS) and causes of late mortality for these patients., Methods: Data between 1973 and 2005 from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Kaplan Meier survival analysis was performed on 5-year survivors of childhood CNS germinomatous germ cell tumors (GGCTs) and nongerminomatous germ cell tumors (NGGCTs). Standardized mortality ratios (SMRs) were calculated using US population data to compare observed versus expected all-cause death and death from stroke. Cumulative incidence was calculated using a competing risk model., Results: Four hundred five GGCTs and 94 NGGCTs cases were eligible. OS at 20 and 30 years for GGCTs was 84.1% and 61.9%, respectively, and was 86.7% for NGGCTs at both time points. Five-year survivors of GGCTs and NGGCTs experienced a 10-fold increase in mortality risk compared with their peers (SMR, 10.41; 95% confidence interval [CI], 7.71-13.76 vs SMR, 10.39;95% CI, 4.83-19.73, respectively). Five-year survivors GGCTs also experienced a nearly 59-fold increase in risk of death from stroke (SMR, 58.93; 95% CI, 18.72-142.10). At 25 years, the cumulative incidence of death due to cancer and subsequent malignancy was 16% and 6.0%, respectively., Conclusion: Although CNS germinomas have favorable cure rates, late recurrences, subsequent malignancies, and stroke significantly affect long-term survival. Close attention to long-term follow-up with assessment of stroke risk factors is recommended., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Survival of children with pineal region tumors has increased significantly in the last decade; these tumors have an insidious outcome associated with endocrine disorders with high morbidity and mortality, especially after gross resection. The objective was to report the survival, outcome, morbidity and mortality according to type of surgery, histology and treatment in children with pineal region tumors., Methods: This retrospective study included all patients of 17 years or less with diagnosis of pineal region tumor, who went over a period of 10 years to a children's hospital. A histopathological review was made, and the extent of resection was determined. The survival was also estimated., Results: Forty-six patients were included, out of which 36 had complete medical records and adequate pathologic material. Gross resection was performed in 24 (66.6 %), and biopsy in 12 (33.3 %); 23 (88 %) patients died; hydroelectrolytic imbalance was the cause of 14 deaths (60 %) and the other nine (39.1 %) were secondary to tumor progression. Ten-years survivals among patients treated with gross resection and biopsy were 52 and 75 %, respectively (p = 0.7). Endocrine alterations were observed in 13 patients (36.1 %); in 10 of these (76.9 %) the total resection was performed., Conclusions: Pineal region tumors in children can be treated with diagnostic biopsy, followed by adjuvant treatment consisting of chemotherapy and radiotherapy.

Aim: To determine the optimal radiotherapy (RT) target volume in correlation with tumor response to chemotherapy in patients with intracranial germinoma., Patients and Methods: Seventy-two patients received chemotherapy followed by RT. The RT field was tailored to chemotherapy response., Results: Five-year recurrence-free survival (RFS) was 87% and overall survival was 97%. RT field was significantly associated with RFS, with 5-year RFS rates of 95%, 91%, and 62% in those who received craniospinal irradiation, whole-brain/whole-ventricle RT, and focal RT, respectively (p=0.01). In the complete-response group after chemotherapy, 5-year RFS rates were 100% after whole-brain RT/whole-ventricle RT and 70% after focal RT (p=0.04). In the partial-response group, 5-year RFS rates after craniospinal irradiation, whole-brain RT, and focal RT were 100%, 85%, and 33%, respectively (p<0.01)., Conclusion: Regardless of response, those treated with focal RT had an excessively high relapse rate. Whole-brain/whole-ventricle RT could be applied to patients who show a complete response to chemotherapy, but the optimal strategy for patients with partial response needs further investigation., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group (p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients (p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival.

Recent advances in diagnostic imaging and experience with germinomas may allow for the differentiation of central nervous system germinomas from other tumors based on clinical information, without histological verification. We retrospectively analyzed clinically diagnosed germinoma-like tumors of the pineal and/or suprasellar regions. This was done to evaluate the efficacy of our strategy of defining germinoma-compatible tumors based on good responses to initial chemotherapy. The responses to chemotherapy and survival of 34 consecutive patients with germinoma-like tumors who underwent initial treatment from July 2001 to October 2010 were analyzed. The minimum apparent diffusion coefficient (minADC) value and proton magnetic resonance spectroscopy (MRS) were evaluated in recent patients. Twelve patients with histologically verified germinomas and 18 with germinoma-compatible tumors showed early logarithmic decreases in tumor volume in response to initial chemotherapy, typical low minADC values and typical MRS characteristics, including increased choline/creatine ratios, decreased N-acetylasparate/creatine ratios, and large lipid peaks. These patients had good progression-free survival. The other four patients, with histologically verified non-germinomas, showed no response to chemotherapy, and one patient with a pineoblastoma showed a similar minADC value and MRS characteristics to those of patients with germinomas. The response to initial chemotherapy can be used to distinguish germinoma-compatible tumors from non-germinoma in patients with germinoma-like tumors of the pineal and/or suprasellar regions. The evaluation of minADC and proton MRS are useful for distinguishing germinomas from other tumors. However, a subset of non-germinomas may show similar characteristics to germinomas. The benefit of bypassing unnecessary surgical intervention can be achieved, at least in Asian populations with a high incidence of germinomas., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: We conducted a nonrandomized international study for intracranial germinoma that compared chemotherapy followed by local radiotherapy with reduced-dose craniospinal irradiation (CSI) alone, to determine whether the combined treatment regimen produced equivalent outcome and avoided irradiation beyond the primary tumor site(s)., Methods: Patients with localized germinoma received either CSI or 2 courses of carboplatin and etoposide alternating with etoposide and ifosfamide, followed by local radiotherapy. Metastatic patients received CSI with focal boosts to primary tumor and metastatic sites, with the option to be preceded with chemotherapy., Results: Patients with localized germinoma (n = 190) received either CSI alone (n = 125) or combined therapy (n = 65), demonstrating no differences in 5-year event-free or overall survival, but a difference in progression-free survival (0.97 ± 0.02 vs 0.88 ± 0.04; P = .04). Seven of 65 patients receiving combined treatment experienced relapse (6 with ventricular recurrence outside the primary radiotherapy field), and only 4 of 125 patients treated with CSI alone experienced relapse (all at the primary tumor site). Metastatic patients (n = 45) had 0.98 ± 0.023 event-free and overall survival., Conclusions: Localized germinoma can be treated with reduced dose CSI alone or with chemotherapy and reduced-field radiotherapy. The pattern of relapse suggests inclusion of ventricles in the radiation field. Reduced-dose craniospinal radiation alone is effective in metastatic disease.

Object: Radiation monotherapy-prophylactic craniospinal or whole-brain irradiation paired with a radiation boost to the primary tumor-is the standard treatment for intracranial germinomas at the authors' institution. The authors assessed long-term outcomes of patients with germinoma who underwent therapy and identified factors affecting them., Methods: The authors retrospectively analyzed data obtained in 46 patients (35 males and 11 females, age 5-43 years at diagnosis) who had been treated for intracranial germinomas between 1990 and 2009 at the authors' institution. Thirty patients had germinomas in localized regions and 16 in multiple regions. Thirty-eight patients (83%) underwent radiotherapy alone (craniospinal irradiation in 32 and whole-brain irradiation in 6). Seven patients underwent radiochemotherapy and 1 underwent chemotherapy alone. The mean radiation doses for the whole brain, spine, and primary tumor site were 26.9, 26.6, and 49.8 Gy, respectively. The median follow-up period was 125 months., Results: The 10-year overall and recurrence-free survival rates were 93.3% and 89.3%, respectively. None of the 38 patients who received radiation monotherapy developed a recurrent lesion, whereas 1 of 7 who underwent radiochemotherapy and the 1 patient who underwent chemotherapy had a recurrent lesion. Of the entire population, 26 patients required hormone replacement therapy, 2 had short stature, and 1 developed a radiation-induced meningioma. Seventeen of the 25 childhood- or adolescent-onset patients were 19 years or older at the latest follow-up visit, 15 of whom graduated from senior high school, and only 2 of whom graduated from college. Of 34 patients who were 19 years or older at the latest visit, 4 were students, 18 worked independently, 4 worked in sheltered workplaces, and 8 were unemployed. Of the 34 patients, 4 got married after the initial treatment, 3 of whom had children. There were 8 patients (17%) with low postoperative Karnofsky Performance Scale (KPS) scores that were significantly associated with impaired neurocognitive functions, severe surgical complications, and neurological impairments. In 10 of the 46 patients, KPS scores at the latest visit were lower than their postoperative KPS scores. These decreases in KPS scores were significantly correlated with a delayed decline in neurocognitive functions in childhood-onset patients and a postoperative impairment of neurocognitive functions in patients with adolescent- or adult-onset germinoma., Conclusions: No tumor recurrence occurred in germinoma patients treated with the authors' radiation monotherapy, which appears to be effective enough to cure the tumor. Brain damage caused by tumors themselves and surgical complications were found to adversely affect functional outcomes in patients regardless of their age. Although radiotherapy rarely caused late adverse effects in patients with adolescent- or adult-onset, in some childhood-onset lesions, the radiation seems to carry the risk of neurocognitive dysfunctions, which are attributable to late adverse effects. Accordingly, treatments for germinoma patients should be selected according to a patient's age and the extent of the tumor and with particular care to avoid surgical complications.

Objective: To analyse the clinicopathologic factors affecting prognosis and fertility of patients with malignant ovarian germ cell tumor (MOGCT)., Methods: The medical records and follow up data of 106 patients with MOGCT treated at Affiliated Tumor Hospital of Guangxi Medical University between January 1986 and December 2010.Kaplan-Meier method was used to analyse survival curves. The different prognoses between different clinicopathologic factor was evaluated by univariate analysis and log-rank test. The multivariate analysis was performed by the Cox proportional hazard regression method. Logistic regression analysis was used to evaluate the influence of different factors on the prognoses and fertility., Results: The median age at primary treatment was 22 years old (range: 9 - 61 years old), 59 patients received fertility-preserving surgery, 45 patients received radical surgery, only 2 cases performed biopsy; 94 patients received postoperative adjuvant chemotherapy. Median follow-up time was 56.5 months (range: 2 - 309 months), there were 11 cases recurrences, 23 cases died from cancer. Of 47 patients live without tumor, 45 patients had normal menstrual. Of the 39 patients desiring pregnancy, 31 cases got 33 successful pregnancies, resulting in 33 live births. There is no statistically significant difference (P > 0.05) in progression free survival (PFS; 67.6% versus 63.3%) and overall survival (OS; 70.0% versus 64.1%) and mortality [15% (9/59) versus 31% (14/45)] between fertility-preserving surgery patients and radical surgery patients. The univariate analysis showed that the pathological types, postoperative residual tumor size, lymph nodes and omental resection were associated with OS (P < 0.1), and postoperative residual tumor size, chemotherapy cycles, lymph nodes and omental resection were associated with PFS (P < 0.1). The multivariate analysis showed only the postoperative residual tumor size was independent prognostic factor of OS (P = 0.039), and postoperative residual tumor size, chemotherapy cycles, lymph nodes resection were independent prognostic factors of PFS (P < 0.05). There is no statistically significant difference in OS, PFS and fertility between fertility-preserving surgery patients treated with or without a comprehensive staging surgery (P > 0.05)., Conclusions: MOGCT can achieve a good prognosis after surgery combined chemotherapy. Postoperative residual tumor size is independent prognostic factor of PFS and OS. Comprehensive staging surgery could not improve prognosis. Fertility-preserving surgery plus adjuvant chemotherapy appeared to have little or no effect on prognosis and fertility.

Purpose: To evaluate whether a multimodal approach including craniospinal irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor (NGGCT) patients., Methods and Materials: We reviewed the records of 32 patients with NGGCTs. Fourteen patients belonged to the intermediate prognosis group (immature teratoma, teratoma with malignant transformation, and mixed tumors mainly composed of germinoma or teratoma), and 18 patients belonged to the poor prognosis group (other highly malignant tumors). Patients with pure germinoma or mature teratoma were excluded from this study. Nineteen patients were treated with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient received RT alone. Twenty-seven patients received CSI with a median of 36 Gy (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole-brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and subtotal resection was 71.9%. The median follow-up for surviving patients was 121 months., Results: Treatment failed in 7 patients. Three of the 5 patients who received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF) failures occurred after CSI. No failure occurred in the intermediate prognosis group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology and CSI were significant prognostic factors for RFS, and CSI was significantly associated with OS., Conclusions: A multimodal approach was effective for treating NGGCTs. CSI should be considered for patients with poor prognostic histology., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial., Methods and Materials: Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded., Results: The median time to recurrence was 30.3 months (range, 3.8-134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2-180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03)., Conclusions: Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective salvage treatment for recurrence after reduced-volume RT., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Previous intracranial germinoma (IG) studies have investigated the effect of different radiotherapy (RT) volumes and the necessity for adjunctive chemotherapy, but there is currently no consensus on the best treatment for this tumor., Methods: From January 1989 to December 2009, 80 IG patients (≤20 years old) were treated with various RT regimens. Of them, 14 patients had craniospinal irradiation (CSI) + primary boost (PB); 8 patients had whole-brain irradiation (WBI) + PB; 31 patients had whole ventricular irradiation (WVI) + PB; and 27 patients had focal RT only. Twenty-nine patients (36.2%) also received systemic chemotherapy (CHT). Survival was estimated by the Kaplan-Meier method and variables affecting survival were analyzed by the Cox proportional hazard model., Results: Eleven patients (13.8%) developed local recurrence or dissemination after treatment, and 10 of these patients were in the focal RT group. The 5-year relapse-free survival (RFS) for the CSI, WBI, WVI, and focal RT patients were 100%, 85.7%, 100%, and 84.6%, respectively (P = .001). The 5-year overall survival (OS) for CSI, WBI, WVI, and focal RT patients was 100%, 83.3%, 100%, and 87.9%, respectively (P = .125). Focal irradiation (P = .02) and initial use of CHT (P = .021) were negatively associated with RFS., Conclusions: Focal RT plus CHT were associated with inferior control of IG and a higher incidence of CHT-related toxicities. Adjustment of the radiation volume to the whole ventricular system without CHT is sufficient for treatment of nondisseminated IGs, even with lower primary RT doses (<36 Gy)., (Copyright © 2011 American Cancer Society.)

OCT4 expresses variably in primary intracranial germinomas. In this study, we tested our hypothesis that such variation of OCT4 is predictive of outcome in primary intracranial germinomas. Thirty-one histologically identified CNS germinoma patients were enrolled in our study. We collected medical data, immunohistochemically evaluated the OCT4 expression level, and followed up all patients from April 2001 to May 2010. We found that 7 of the 31 patients expressed OCT4 weakly, 11 expressed OCT4 moderately, and 13 expressed OCT4 strongly. No significant correlation between the OCT4 expression level and clinicopathological characteristics was observed. WV-CS combined treatment modality showed a better 5-year progression-free survival (PFS) rate than other treatment modalities and a low expression level of OCT4 showed a significantly better 5-year PFS. In both the WV-CS combined treatment modality and other treatments modality group, patients received a better 5-year PFS and had a lower level of OCT4 expression. As a result, we suggest OCT4 as a probable prognostic marker for intracranial germinoma.

Purpose: Initially disseminated intracranial germinomas (IDIGs) can be observed in pre-adult and adolescent brain tumor patients. However, the disease prognosis is undetermined, and the method of optimal treatment remains controversial., Methods: From January 1990 to January 2011, data on 91 intracranial germinoma patients (≤20 years old) were gathered from the Pediatric Brain Tumor database at Taipei Veterans General Hospital. A total of seven patients with a median age of 17.0 years had IDIGs (lesion sites >2), including IDIGs in the ventricular system or the spinal column. Craniospinal irradiation (CSI) plus a primary or metastatic boost was the mainstay strategy for radiotherapy. Six out of a total of seven patients (85.7%) also received systemic chemotherapy (CHT) after radiotherapy. Survivals rates between IDIGs and patients without dissemination were estimated using the Kaplan-Meier method., Results: The median follow-up time for all seven patients was 67.5 months (range, 10.3-142.3 months). None of the IDIG patients experienced a recurrence or mortality after the completion of treatment. The 5- and 10-year disease-free survival (DFS) between IDIG and non-dissemination patients were 100%, 100%, 93.0% and 78.6%, respectively (p = 0.339). The 5- and 10-year overall survival (OS) between IDIGs and non-dissemination cases were 100%, 100%, 93.7% and 89.4%, respectively (p = 0.473)., Conclusions: IDIG patients did not show reduced survival compared to non-dissemination patients if optimal radiotherapy and chemotherapy were used together.

Testicular cancer is the most common solid organ malignancy in young men between the ages of 15 and 35. Although much of this increase in survival can be attributed to improvements in systemic chemotherapy, surgery retains a critical role in the diagnostic and therapeutic management of testicular cancer. Laparoscopic retroperitoneal lymph node dissection is an effective staging and therapeutic procedure in patients with low-stage testicular cancer. It is an attractive alternative to the open approach, with faster recovery, improved cosmesis, and reduced post-operative morbidity driving its application. In experienced hands, it can be used in postchemotherapy patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Retroperitoneal lymphadenectomy remains an integral component in the multidisciplinary management of testicular cancer. Through the evolution of the procedure, continued refinements have led to diagnostic and therapeutic benefits as well as improvements in perioperative and long-term morbidity. This article discusses the surgical management of testicular cancer, specifically addressing the indications, controversies, and complications of retroperitoneal lymph node dissection for both low-stage and high-stage disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost., Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case., Results: Twenty-two patients were treated with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes., Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose of Review: Various approaches have been used for the management of patients with germ cell tumors (GCTs) in the central nervous system (CNS); however, the optimal treatment of both germinoma and nongerminomatous GCTs remains unknown. This review discusses current management strategies and late effects of therapy for CNS GCTs., Recent Findings: To reduce the late complications of radiation therapy for patients with germinoma, many investigators have introduced dose reduction of radiation therapy in association with platinum-based chemotherapy. In addition, the radiation field has been restricted to the whole ventricular area for localized germinoma. This type of combination therapy has shown promising results and preserves cognitive function and quality of life. Despite various approaches including high-dose chemotherapy against highly malignant or relapsed GCTs, the prognoses of these patients remain dismal except for a few successful reports., Summary: The 10-year survival rate of CNS germinoma is approximately 90%. Most patients with CNS GCTs are children and young adults. Therefore, with the improving life prognosis of young patients, secondary neoplasms, secondary cerebral vasculopathy, neurocognitive deficits, and many other adverse effects induced by the initial treatments are problems to be solved in the next decade.

Purpose: To update our institutional experience with neoadjuvant chemotherapy and minimized radiotherapy vs. radiation monotherapy for intracranial germinoma., Methods and Materials: We retrospectively reviewed records of 59 patients with diagnosis of primary intracranial germinoma between 1977 and 2007. Treatment was irradiation alone or neoadjuvant platinum-based chemotherapy and local irradiation (initial tumor plus margin) for patients with localized complete response and reduced-dose craniospinal irradiation for others., Results: For the chemoradiotherapy group (n = 28), median follow-up was 7 years. No patient died. The freedom from progression (FFP) rate was 88% at 5 years and 80% at 10 years. In 4 patients, disease recurred 1.1 to 6.8 years after diagnosis. All were young male patients who received 30.6 Gy to local fields after complete response to chemotherapy. The FFP rate was 88% for local irradiation vs. 100% for more extensive fields (p = .06). For the radiotherapy-alone group (n = 31), median follow-up was 15 years. Overall and disease-free survival rates were 93% and 93% at 5 years and 90% and 87% at 15 years. In 5 patients, disease recurred 1.1 to 4.9 years after diagnosis. Most patients in this group were young men 18 to 23 years of age with suprasellar primary disease treated with about 50 Gy to local fields. The FFP rate was 44% for local irradiation vs. 100% for more extensive fields (p < .01)., Conclusions: The addition of neoadjuvant chemotherapy to local-field radiotherapy reduced central nervous system cancer recurrence when high-risk patients were excluded by thorough pretreatment staging. There was trend toward improved central nervous system tumor control when larger fields (whole brain, whole ventricle, or craniospinal axis) were used., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To review the effectiveness of reduced-dose and restricted-volume radiation-only therapy in the treatment of intracranial germinoma and to assess the feasibility of reducing or eliminating the use of chemotherapy., Methods and Materials: Between January 1996 and March 2007, a retrospective analysis was performed that included 38 patients who received either reduced radiation alone (30 Gy for 26 patients) or reduced radiation with chemotherapy (n = 12 patients). All 38 patients received extended focal (including whole-ventricle) irradiation and were followed up until February 2008. Overall survival (OS) and relapse-free survival (RFS) rates were calculated. Variables associated with survival were evaluated by univariate Cox proportional hazards regression., Results: Median follow-up was 62.4 months (range, 10.1-142.5 months). The total 5-year OS rate was 93.7%. The 5-year OS and RFS rates for patients receiving radiation only were 100% and 96.2%, respectively. The rates for those receiving radiation plus chemotherapy were 83.3 % and 91.7%, respectively (not statistically significant). No predictive factor was significantly associated with the OS or RFS rate. Chemotherapy had no significant effect on survival but was associated with a higher incidence of treatment-related toxicity., Conclusions: A further decrease in the radiation dose to 30 Gy with whole-ventricle irradiation is sufficient to treat selected patients with intracranial germinoma. Wide-field irradiation or chemotherapy should be avoided as these methods are unnecessary. Thus, reduction of the radiation dose to 30 Gy may be feasible, even without chemotherapy., (Copyright 2010 Elsevier Inc. All rights reserved.)

Postchemotherapy retroperitoneal lymph node dissection (RLND) was performed in 70 testicular non-seminoma patients with elevated serum tumor markers (age median 27.0 +/- 8.1 years) from 1983 to 2008. N1, N2, N3, Nx were diagnosed in 4 (5.7%), 10 (14.3%), 35 (50.0%), 21 (30.0%) patients. Distant metastases were present in 23 (32.9%) cases. The level of the initial tumor markers was elevated in all the patients: S1 - 169 (46.0%), S2 - 108 (29.4%), S3 - 51 (13.9%), Sx - 39 (10.6%). According to the IGCCCG prognostic model, 11 (15.7%) patients were classified as good, 19 (27.1%)--as moderate, 16 (22.9%)--as poor prognostic groups. The prognostic group was not identified in 24 (34.3%) cases which started treatment in other hospitals. All the patients received induction cisplatin-based chemotherapy following orchidectomy (first-line--24 (34.3%), second-line--46 (65.7%) which resulted in tumor shrinkage < 50% in 7 (10.0%), 51-90% in 23 (32.9%), > 90%--in 2 (2.9%) cases. The response was not properly assessed in 38 (54.3%) cases. CT scan revealed residual retroperitoneal masses after chemotherapy in all the patients: < 2 cm--5 (7.1%), 2-5 cm--25 (35.7%), > 5 cm--40 (57.1%). The level of the tumor markers remained positive in all the patients. Further chemotherapy was not perspective in all 70 patients who further underwent retroperitoneal lymph node dissection (RLND). Radical RLND was performed in 59 (84.3%) patients. Postoperative chemotherapy was given to 27 (38.6%) cases. Median follow-up was 20.8 (3-137) months. Complications developed in 12.9% (9/70) patients. Mortality was 1.4% (1/70). Histology revealed necrosis in 20 (28.6%), teratoma--in 26 (37.1%), cancer--in 24 (34.3%) specimens. Prognostic factors for cancer in retroperitoneal pathology were the following: S > S1 (p = 0.013), intermediate or poor prognosis group IGCCCG (p = 0.014), absence of embryonal carcinoma (p = 0.003), the presence of choriocarcinoma in the testicular tumor (p = 0.028), second-line chemotherapy (p = 0.001), residual mass > 2 cm (p = 0.006). Five-year overall, specific and progression-free survival of 70 patients was 41.0%, 42.4% and 31.8%, respectively. Univariate analysis revealed an adverse impact on progressive-free survival of category S > S1 (p = 0.015), intermediate or poor prognostic group IGCCCG (p = 0.01), the presence of embryonal carcinoma (p = 0.020) and the absence of choriocarcinoma in the testicular tumor (p = 0.029), tumor shrinkage < 50% (p < 0.0001), incomplete RLND (p = 0.012), an incomplete effect of the combined treatment (p < 0.0001), cancer in the residual mass (p < 0.0001). The multivariate analysis proved predictive value of an incomplete effect of the combined treatment (p < 0.0001). Thus, selected testicular non-seminoma patients with elevated serum tumor markers are curable with surgery. The best candidates for RLND in this group are patients without a tumor markers level increase during chemotherapy, with S1 category, good IGCCCG prognosis, tumor shrinkage > 50% and potentially respectable residual disease.

Objectives: Testicular cancer is the most common cancer in men age 25 to 35 years. We examined therapy, compliance with guidelines, and survival in a population based sample of men newly diagnosed with testicular cancer., Materials and Methods: We analyzed the National Cancer Institute's (NCI) patterns of care data on 702 men diagnosed with testicular cancer in 1999. These studies supplement routine data collection by verifying therapy with the patients' treating physicians. Follow-up for vital status was available through December 31, 2004., Results: The majority of the men with seminoma were diagnosed while their cancer was localized and more than 80% of received orchiectomy with radiation. For men with seminoma and nonseminoma germ cell tumors (NSGCT), the percent receiving chemotherapy increased markedly as stage increased. More than 90% of men with regional and distant NSGCT received chemotherapy. Less than 25% of men with localized NSGCT received orchiectomy and retroperitoneal lymph node dissection (RPLND), about 40% had surveillance following an orchiectomy alone, and 30% received orchiectomy and chemotherapy., Conclusions: The majority of these patients received therapy consistent with guidelines. While there was no significant difference in the use of RPLND in men with localized NSGCT by geographic region, chemotherapy use varied widely. Over 90% of men with localized or regional disease diagnosed in 1999 were alive at the end of 2004. The excellent survival rates point to the need to monitor for late effects of therapy.

Background: Adults and children with recurrent malignant central nervous system (CNS) tumors have a poor prognosis despite high dose chemotherapy with a conventional stem cell rescue regimen. In this study we evaluated the results of low dose, continuous infusion etoposide over 21 days added to a conventional high-dose regimen of carboplatin and thiotepa in eight patients with relapsed pediatric CNS tumors., Procedure: Patients with high risk CNS tumors were treated with etoposide 25 mg/m(2)/day by continuous intravenous (IV) infusion from day -22 to day -2, carboplatin 667 mg/m(2)/dose IV (or area under the curve = 9 mg/ml/min according to the Calvert formula on days -8, -7, and -6, and thiotepa 300 mg/m(2)/dose IV on days -5, -4, and -3, followed by autologous hematopoietic stem cell rescue on day 0., Results: Eight adults and children, with a mean age of 12.9 years (age range 5.6-27.8 years), with relapsed primary CNS tumors (metastatic medulloblastoma (7), germinoma (1)), were enrolled. The mean survival post-transplant was 4.8+ years, (range 8-160+ months). The 2- and 5-year overall survival rates were 75% and 50% respectively. None of the survivors required additional salvage irradiation., Conclusion: The strategy of low dose chronic exposure to a topoisomerase inhibitor along with ablative carboplatin and thiotepa with stem cell rescue showed promising survival outcomes in these relapsed patients. This treatment strategy deserves further evaluation in a larger group of high-risk or relapsed primary CNS tumors., (Copyright 2009 Wiley-Liss, Inc.)

Purpose: To assess the quality of life (QOL) of extremely long-time survivors with germinoma mainly treated with radiotherapy., Patients and Methods: We enrolled 52 of 68 patients who received radiotherapy between 1968 and 1995 at our hospital. They were 41 males and 11 females; the tumor location was pineal in 20, neurohypophyseal in 15, pineal and neurohypophyseal in 11 patients; in 6 it was located in another region. All underwent radiotherapy; the median dose was 48.2 (range 40.0-60.2) Gy. The median follow-up period was 226 (range 0-448) months. The clinical outcome and QOL were evaluated retrospectively., Results: In 6 patients, the tumor recurred; 6 other patients developed second tumors while in complete remission from the first tumor. The main cause of 12 deaths was complications due to primary tumor invasion, the initial treatment, or tumor recurrence rather than tumor progression. The 10-, 20-, and 30-year actuarial survival rate was 83.6, 77.5, and 64.2%, respectively. Of 44 patients, 6 were married and 3 males with solitary pineal tumors were fathers. Among 32 patients, 14 had, or had not, graduated from high school; the other 18 went on to higher education. Twenty-one patients had no occupation; 7 of 11 formerly employed patients had left their jobs., Conclusion: Radiotherapy delivered between 1968 and 1995 to patients with germinoma yielded satisfactory outcomes but a decline in the QOL., (Copyright (c) 2009 S. Karger AG, Basel.)

Objects: To evaluate the disease characteristics and treatment outcomes for patients with intracranial synchronous bifocal germinomas treated with extended focal irradiation alone., Methods: Between January 1996 and March 2007, seven patients (three males and four females) with intracranial synchronous bifocal germinomas treated at Taipei Veterans General Hospital were reviewed. The median age at diagnosis was 14 years (range, 11-28 years). Four patients had surgery before radiotherapy. All patients underwent extended focal irradiation encompassing the whole ventricle system with a total radiation dose of 30 Gy (2 Gy daily). No patient received scheduled systemic chemotherapy before or after radiotherapy. Disease characteristics, treatment outcomes, and the impact of lesion numbers (single vs. bifocal) on survivals were investigated., Results: With a median follow-up time of 49 months (range, 20-66 months), the 2- and 5-year survival rates were both 100%. After treatment, all patients had good performance without recurrence. No severe complication was observed. In comparison, the overall survival (OS, p = 0.475) and the disease-free survival (DFS, p = 0.537) rates were not significantly different between bifocal- and single-lesion groups. Lesion numbers did not affect both OS and DFS. In addition, the incidence of neuraxial seeding was not higher in patients with bifocal germinomas as compared to those with single lesion., Conclusions: Intracranial germinomas are extremely radiosensitive. Young patients with synchronous bifocal germinomas could be successfully treated with extended focal 30-Gy radiotherapy alone. The therapeutic advantage using this regimen needs to be further evaluated with larger sample size and longer follow-up time.

Central nervous system (CNS) germinoma is a curable tumor and its recurrence rate after initial therapy may be approximately 10% or higher. This study elucidates the time-course of recurrence and results of salvage therapy. Twenty-five patients with recurrent germinoma treated at Hokkaido University Hospital were retrospectively reviewed. The median age at initial treatment was 12 years (range: 8-37). All patients had been tumor-free for at least 6 months after the initial treatment. The median follow-up period was 134 months (range: 44-338). The median age at first recurrence was 18 years and the median time to the first recurrence was 50 months. Among the patients, 9 (36%) had the first recurrence at 60 months or later. The latest recurrence in a patient occurred 230 months after the initial treatment. The results of salvage therapy were estimated in all 25 patients. Seventeen patients (68%) were salvaged and were tumor-free at the final observation. The remaining 8 patients died of disease. At first recurrence, 11 patients were treated using radiation therapy with or without surgery and 7 out of the 11 patients died due to the recurrent tumor. On the other hand, 13 patients who received salvage chemotherapy and radiotherapy were tumor-free at the last follow-up. In conclusion, late recurrence is not a rare event in patients with CNS germinoma. To identify a true cure rate of this disease, a 10-year or longer observation period may be required. As a salvage therapy, platinum-based chemotherapy followed by wide-field low-dose radiation therapy appears to be effective.

Purpose: We evaluated the feasibility and early oncological outcome of a laparoscopic nerve sparing bilateral retroperitoneal lymph node dissection. The surgical technique is described., Materials and Methods: From July 2004 to December 2007 a total of 42 patients with nonseminomatous germ cell tumor (21 with stage I, 2 with stage IIA marker negative and 19 with post-chemotherapy stage IIB disease) underwent transperitoneal bilateral laparoscopic retroperitoneal lymph node dissection. The sympathetic trunk and postganglionic nerves were identified, and lymphatic tissue was dissected between the nerves. Patients with clinical stage I and IIA disease that was lymph node positive at laparoscopic retroperitoneal lymph node dissection did not receive additional chemotherapy., Results: Surgery was successfully completed in all patients and no conversion to open surgery was necessary. Mean operative time was 323 minutes. No intraoperative complications occurred. Of patients with stage I and marker negative stage IIA disease active tumor was found in 5 retroperitoneal lymph node dissection specimens, and no patients had recurrence. Of 19 patients with post-chemotherapy stage IIB disease teratoma was found in the lymphatic tissue in 4 (21.0%). No retroperitoneal recurrence was observed. Pulmonary metastases developed 9 months after surgery in 1 patient with stage I disease and negative retroperitoneal histology, and were treated successfully. All patients are currently free of disease at a mean followup of 17.2 months. Antegrade ejaculation was preserved in 36 patients (85.7%)., Conclusions: Bilateral nerve sparing laparoscopic retroperitoneal lymph node dissection is feasible and associated with low morbidity if performed by experienced hands. The oncological efficacy of this approach is promising and currently under evaluation.

Purpose: To retrospectively compare the outcome of upfront chemotherapy plus radiotherapy (CRT) and the outcome of the use of extended radiotherapy (RT) only for intracranial germinoma., Methods and Materials: Of 81 patients with tissue-confirmed intracranial germinoma, 42 underwent CRT and 39 underwent RT only. For CRT, one to five cycles of upfront chemotherapy was followed by involved-field or extended-field RT, for which the dose was dependent on the M stage. For RT only, all 39 patients underwent craniospinal RT alone. The median follow-up was 68 months., Results: The 5- and 10-year overall survival rate was 100% and 92.5% for RT alone and 92.9% and 92.9% for CRT, respectively. The 5-year recurrence-free survival rate was 100.0% for RT and 88.1% for CRT (p = 0.0279). No recurrences developed in patients given RT, but four relapses developed in patients who had received CRT -- three in the brain and one in the spine. Only one patient achieved complete remission from salvage treatment. The proportion of patients requiring hormonal replacement was greater for patients who received RT than for those who had received CRT (p = 0.0106)., Conclusions: The results of our study have shown that the better quality of life provided by CRT was compensated for by the greater rate of relapse. The possible benefit of including the ventricles in involved-field RT after upfront chemotherapy, specifically for patients with initial negative seeding, should be addressed in a prospective study.

Background: Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes., Patients and Methods: The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas., Results: Mean age at diagnosis was 19.7 years (range 15-32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40-54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7-27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case., Conclusion: Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Supported by experimental evidence and convincing results of early phase II studies, since the 1980s high-dose chemotherapy (HDC) with autologous hematopoietic stem cell support (AHSCT) has been uncritically adopted by many oncologists as a potentially curative option for several solid tumors. As a result, the number (and size) of randomized trials comparing this approach with conventional chemotherapy initiated (and often abandoned before completion) in this setting was limited and the benefit of a greater escalation of dose of chemotherapy with stem cell transplantation in solid tumors remains, with the possible exception of breast carcinoma (BC) and germ cell tumors (GCT), largely unsettled. In this article, we review and comment on the data from studies to date of HDC for solid tumors in adults.

Purpose: There are several management options for patients with clinical stage I (CS1) nonseminomatous germ cell tumors (NSGCT); this study examined whether an 18fluorodeoxyglucose positron emission tomography (18FDG PET) scan could identify patients without occult metastatic disease for whom surveillance is an attractive option., Methods: High-risk (lymphovascular invasion positive) patients with CS1 NSGCT underwent 18FDG PET scanning within 8 weeks of orchidectomy or marker normalization. PET-positive patients went off study; PET-negative patients were observed on a surveillance program. The primary outcome measure was the 2-year relapse-free rate (RFR) in patients with a negative PET scan (the negative predictive value). Assuming an RFR of 90% to exclude an RFR less than 80% with approximately 90% power, 100 PET-negative patients were required; 135 scanned patients were anticipated., Results: Patients were registered between May 2002 and January 2005, when the trial was stopped by the independent data monitoring committee due to an unacceptably high relapse rate in the PET-negative patients. Of 116 registered patients, 111 underwent PET scans, and 88 (79%) were PET-negative (61% of preorchidectomy marker-negative patients v 88% of marker-positive patients; P = .002); 87 proceeded to surveillance, and one requested adjuvant chemotherapy. With a median follow-up of 12 months, 33 of 87 patients on surveillance relapsed (1-year RFR, 63%; 90% CI, 54% to 72%)., Conclusion: Though PET identified some patients with disease not detected by computed tomography scan, the relapse rate among PET negative patients remains high. The results show that 18FDG PET scanning is not sufficiently sensitive to identify patients at low risk of relapse in this setting.

Background: The authors compared the patterns of failure in patients with intracranial germinoma who were managed with either chemotherapy and focal irradiation or with craniospinal irradiation (CSI)., Methods: A retrospective review was conducted on 21 patients with intracranial germinoma and treated with radiotherapy (RT) to the central nervous system at The University of Texas M. D. Anderson Cancer Center from 1981 to 2002. The study group was comprised of 13 males and 8 females with a median age at diagnosis of 19 years. Nine patients received chemotherapy prior to focal RT. Twelve patients received CSI., Results: The actuarial 10-year survival rate for all patients was 86%. The overall survival rate at 10 years was 89% for patients who received focal RT and 83% for patients who received CSI (P = .73). The 10-year local control rate in the brain for patients who received focal irradiation was 59% compared with 100% for patients who received CSI (P = .08). The rate of distant control in the spine at 5 years was 62% for patients who received focal irradiation and 100% for patients who received CSI (P = .04)., Conclusions: Although focal techniques of irradiation with chemotherapy are attractive methods that limited the volume irradiated, the strategy appeared to be associated with increased rates of failures in the brain and spine., ((c) 2006 American Cancer Society.)

Background: Growth hormone (GH) has been used successfully in the treatment of short stature secondary to GH deficiency in survivors of childhood brain tumours. There has been concern that GH might increase the risk of recurrence., Aim: To analyse KIGS (Pfizer International Growth Database) with respect to tumour recurrence in patients with brain tumours., Methods: Data for tumour recurrence were analysed retrospectively in 1038 patients with craniopharyngiomas, 655 with medulloblastomas, 113 with ependymomas, 297 with germinomas, and 400 with astrocytomas or gliomas. All patients had received recombinant human GH (Genotropin, Pfizer Inc.)., Results: Recurrence-free survival rates were 63% at a follow-up of 10.3 y in craniopharyngioma, 69% in 9.1 y in the glial tumours, 71% in 7.4 y in germinomas, 92% in 4.6 y in medulloblastomas and 89% in 2.5 y in ependymomas. Dose of GH and treatment modalities did not differ significantly between patients with and without recurrence., Conclusion: Tumour recurrence rates in surviving patients with brain tumours receiving GH treatment do not appear to be increased compared with published reports. However, longer follow-up regarding recurrences and secondary neoplasms remains essential.

Background: Combination of bleomycin, etoposide and cisplatin (BEP) remains the standard chemotherapy for testicular cancer. Since the development of BEP in the 1980s, there has been a considerable advance in supportive therapies, such as granulocyte colony-stimulating-factor and 5-HT3 antagonists. Therefore, we re-evaluated the completion and toxicity of BEP combined with modern supportive care., Methods: The medical records of all 42 testicular cancer patients who received induction chemotherapy at Tsukuba University Hospital were reviewed. Toxicities during the induction chemotherapy were graded according to the Japanese CTCAE v3.0., Results: Dose reduction was needed in only three patients. The subsequent chemotherapy was started at the planned 3 week interval or within 3 days of postponement in 89% of the treatment cycles. The average relative dose intensity (RDI) of bleomycin was 0.95, while that for etoposide and cisplatin was 0.97. There was no death due to toxicity. The most frequent toxicity was leukopenia (grade 3 in 44% and grade 4 in 55%). Post-chemotherapy diffusion capacity was significantly decreased in 30% of patients. Two patients developed bleomycin-induced pneumonitis, but recovered successfully. Sixteen patients received second line or salvage chemotherapy after BEP, subsequently. The overall 5 year cause-specific survival rate was 85%., Conclusion: BEP with high RDIs is acceptable if combined with modern supportive care, with acceptable toxicity profile in most patients.

Objective: To evaluate the impact of fertility-saving surgery and adjuvant chemotherapy on survival and fertility of young patients with ovarian malignant tumors., Methods: A retrospective analysis was done on 38 patients with ovarian malignant germ cell tumors, 22 patients with malignant epithelial tumors and 4 patients with sexual cord mesenchymal tumors receiving conservative treatments. Outcomes such as menstruation and reproduction ability were assessed., Results: Fifty-nine among 64 patients have been alive up to now (92%). The overall survival rate for ovarian epithelial malignancies, malignant germ cell tumors and sexual cord mesenchymal tumors were 95% (21/22), 89% (34/38) and 4/4, respectively. Fifteen patients received second operation and recurrence was found in 6 patients. Among the 59 surviving patients, 53 had normal menstruation. Thirteen patients among 20 patients who wanted to get pregnant had 15 pregnancies and 9 successful deliveries., Conclusions: The management of fertility-saving surgery on patients with ovarian malignant germ cell tumors, whatever the stagings are, is a safe option. For patients with ovarian epithelial carcinomas, fertility-saving surgery is only indicated for low-stage (stage I), high-grade (G1), and patients who hope to maintain fertility function eagerly. Cisplatinum-based combination chemotherapy is necessary. Standardized chemotherapy has no effect on fertility function.

Between 1975 and 2005, we treated 52 newly diagnosed germinoma patients. Until 1991, patients with pure germinomas or germinomas with syncytiotrophoblastic giant cells (STGCs) received whole-brain radiotherapy only. Of the 52 patients, 30 were treated with a reduced radiation volume and combined chemotherapy; seven of these received local irradiation with 24 Gy, two received whole-brain (30 Gy) plus local irradiation (20 Gy), 16 received extended local irradiation delivered to the whole ventricles (30 Gy) plus local (20 Gy) irradiation, and five received extended local irradiation (24 Gy). Of the 30 patients treated with a reduced radiation volume and combined chemotherapy, four experienced tumor recurrence; three patients had been treated with 24 Gy of local radiotherapy and one had received extended local (30 Gy) plus local (20 Gy) irradiation in addition to chemotherapy. In these patients, the delivered radiotherapy was inadequate and the origin of the recurrent tumors was outside the radiation field. None of the patients who had received at least 24 Gy of whole ventricle radiotherapy combined with chemotherapy experienced tumor recurrence. In combination with chemotherapy, the delivery of irradiation covering the ventricles effectively reduced the incidence of tumor recurrence in patients with germinomas or germinomas with STGCs.

Objective: To evaluate the impact of lymphadenectomy on the relapse and survival of malignant ovarian germ cell tumor (OGCT)., Methods: The clinical data of 102 OGCT cases treated in Peking Union Medical College Hospital from June 1980 to June 2003 were analyzed retrospectively. All the data about lymphadenectomy during primary and secondary surgery were collected, and other factors related to prognosis were also collected at the same time. Chi-squared test was applied in the univariate analysis related to relapse of disease. Cox model was applied in multivariate analysis related to relapse and survival of disease., Results: Pelvic and paraaortic lymph node metastasis was not significantly related to prognosis in primary and secondary treated patients. Lymphadenectomy showed no significant impact on disease relapse and survival. In the primary treatment, International Federation of Gynecology and Obstetrics (FIGO) staging, chemotherapy regimen, residual tumor and lymphadenectomy were the significant factors related to the relapse. After being stratified for the chemotherapy regimen, lymphadenectomy was not significantly related to the relapse in bleomycin +etoposide +cisplatin or cisplatin +vincristine +bleomycin regimen group, and lymphadenectomy could prevent relapse in no chemotherapy or other chemotherapy regimen group. In relapsed patients, only residual tumor was significantly related to survival time after relapse., Conclusions: Pelvic lymph node metastasis is not the significant risk factor related to prognosis. Lymphadenectomy may have a beneficial effect on survival, although such effect is not significant. Although lymphadenectomy provides important information for prognosis, they provide little benefit to those patients already requiring chemotherapy based on the original operative findings. Lymphadenectomy should be performed to primary or relapsed patients by an expert surgical team.

The standard therapeutique approach to patients with advanced germ cell tumors of the testis is a combination of systemic chemotherapy with surgical removal of the residual disease. The indication of surgery, residual tumor resection (RTR) or retroperitoneal lymph node dissection (RPLND), has changed during the last 10 years. Sugery is not longer recommended after chemotherapy of pure seminoma and surveillance of the residual tumor is the favored option. RPLND is a critical component of the treatment armentarium in low-stage nonseminomatous germ cell. RPLND is an accurate staging tool prviding important information to dtermine the need for chemotherapy. When performed properly, RPLND eliminates the retroperitoneum as a site for relapse, wich in turn provides emotional and psychological relief to the patient, and simplifies the follow-up protocol. In advanced nonseminomatous tumours, surgery after chemotherapy is recommended in most of the cases since large studies have shown that a considerable proportion of patients with complete radiological remission after chemotherapy harbor vital carcinoma or teratoma. Prediction models of necrosis after chemotherapy in order to avoid RTR are generally accepted since the accuracy of most models is too low. RTR is indicated in patients with elevated markers after two different chemotherapy regimens (including salvage chemotherapy) either to resect teratoma or cystic residual disease or to remove chemorefractory disease. Laparoscopic approache is a viable staging tool; however, oncologic control of the retroperitoneum has not been reliably determined.

Purpose: The efficacy of paclitaxel was evaluated in combination with ifosfamide and cisplatin as second-line chemotherapy for patients with relapsed testicular germ cell tumors (GCTs)., Patients and Methods: Forty-six patients with progressive metastatic GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. Eligibility required that patients have both a testis primary tumor site and a prior complete response (CR) to a first-line chemotherapy program, which had been identified previously as favorable prognostic factors to conventional-dose salvage chemotherapy., Results: Thirty-two (70%) of 46 patients achieved a CR to treatment. Three patients (7%) who achieved a CR relapsed after TIP chemotherapy. Twenty-nine patients are continuously disease free at a median follow-up time of 69 months, resulting in a 63% durable CR rate and a 2-year progression-free survival rate of 65% (95% CI, 51% to 79%)., Conclusion: Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.

Objective: To evaluate the role of postchemotherapy adjunctive surgery in patients with liver metastases from germ cell cancer (GCT)., Patients and Methods: Forty-three male patients with nonseminoma were treated in different multicenter treatment protocols between 1990 and 1999, and they underwent hepatic surgery. The results of postchemotherapy surgical resection, histologic findings found during postchemotherapy surgery, and prognostic factors for survival were assessed., Results: Thirty-five of 43 patients (81%) were initially diagnosed with liver metastases and advanced GCT, and 8 patients (19%) presented with metachronous liver metastases after a median interval of 16 months (range, 6-103 months). Twelve patients (28%) had isolated liver metastases after completion of chemotherapy, while 31 patients (72%) had additional residual extrahepatic tumor masses. Liver surgery included tumor excision or segmentectomy in 32 patients (74%) and hepatectomy (right/left) or resection of multiple segments in 11 patients (26%). Histologic analysis of postchemotherapy resected residua yielded necrosis in 67%, teratoma in 12%, and viable cancer in 21%. Additional resections at other sites have been performed in 31 patients revealing necrosis in 61% (n = 19), teratoma in 29% (n = 9), and vital carcinoma in 10% (n = 3). In 39% of patients, histologic findings differed among liver and other resection sites. Refractoriness to chemotherapy was associated with a shorter survival after surgery, and a trend was seen in patients with elevation of AFP., Conclusion: The high rate of viable cancer and teratoma found in liver specimens, differing histologic results at residual tumor locations, and the high survival rate achieved support a multidisciplinary approach including resection of liver masses since no accurate selection of patients can narrow the use of surgery.